Proteoglycans are proteins that have glycosaminoglycans attached to them. The structure and function of proteoglycans varies greatly from one proteoglycan to another, but several of them are extracellular matrix components involved in cell adhesion. The biological and medical importance of cell adhesion has led us to charact3erize proteoglycans in this project. We have cloned the cDNAs of three different proteoglycan core proteins. These cDNAs will now be used in this component and in component IV to study the structure-function relationships in the proteoglycans. The complete proteoglycans, the core proteins and truncated forms of the core proteins will be expressed from cDNA constructs in mammalian cells and the functions of the products will be studied by various assays. Specifically, the function of the lectin-like and epidermal growth factor-like domains found in the core protein of the large fibroblast proteoglycan PG 350 will be studied by binding assays and by observing effects of the expression of these domains on cells expressing them. The latter type of experiment has recently given an important clue to the function of another proteoglycan, decorin. We have found that cells expressing decorin have a much flatter morphology and grow to a lower saturation density than cells containing the expression vector alone. These findings suggest that decorin may be at least partially responsible for the "contact inhibition of growth" phenomenon. Moreover, since decorin is one of the extracellular matrix molecules the synthesis of which is increased by transforming growth factor beta, the inhibitory effect of this factor on the proliferation of some types of cells may be mediated by decorin. This possiblity and the mechanism of the decorin effect on cells will be explored in this component. Important information on the growth characteristics of cells and on proteoglycan functions should ensue.